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15 pages, 7271 KB  
Article
Application of ECIS to Evaluate the Effects of Porcine Urinary Bladder Matrix Hydrogels on Caco-2 Cell Attachment, Migration, and Barrier Formation
by Wei-Ling Chen, Chi-Tien Chen, Huynh-Quang-Dieu Nguyen, Phenpitcha Charoensaensuk, Chen-Yu Kao and Chun-Min Lo
Gels 2026, 12(6), 552; https://doi.org/10.3390/gels12060552 (registering DOI) - 19 Jun 2026
Viewed by 64
Abstract
Recent studies have highlighted the potential of urinary bladder matrix (UBM) derived from decellularized porcine urinary bladder as a bioactive hydrogel. Despite its complex composition of over 100 proteins, Type I collagen is the primary constituent of UBM. Caco-2 cells are widely used [...] Read more.
Recent studies have highlighted the potential of urinary bladder matrix (UBM) derived from decellularized porcine urinary bladder as a bioactive hydrogel. Despite its complex composition of over 100 proteins, Type I collagen is the primary constituent of UBM. Caco-2 cells are widely used as an in vitro model of the intestinal epithelium; however, to date, no published study has evaluated the effects of UBM on Caco-2 cells. In this study, Electric Cell–Substrate Impedance Sensing (ECIS) was used to measure Caco-2 cell attachment and wound-healing migration on UBM-coated microelectrodes. Our results demonstrate that UBM hydrogel coating at 0.2 mg/mL significantly accelerates cell attachment and enhances migration rates compared to uncoated controls. These stimulatory effects were comparable to those observed with 0.2 mg/mL Type I collagen, suggesting that UBM can function as effectively as Type I collagen. We further monitored barrier formation in Caco-2 cells cultured on UBM-coated transwell membrane inserts using TEER measurements and scanning electron microscopy. The TEER values reached 300 Ω·cm2 within three days, indicating the rapid establishment of mature tight junctions. Overall, these results show that UBM hydrogel coatings are effective substrates for Caco-2 cells, performing as well as Type I collagen in all our tests. Full article
(This article belongs to the Special Issue Advances in Hydrogels for Regenerative Medicine (2nd Edition))
31 pages, 505 KB  
Review
From Regenerative Mechanisms to Clinical Practice: Current Status, Controversies, and Future Perspectives of Platelet-Rich Plasma in Urology and Sexual Medicine
by Rui Qu, Jiaqi Gu, Yi Luo, Luo Yang and Yi Dai
J. Clin. Med. 2026, 15(8), 2949; https://doi.org/10.3390/jcm15082949 - 13 Apr 2026
Cited by 1 | Viewed by 805
Abstract
Background/Objectives: Platelet-rich plasma (PRP) is an autologous blood-derived biologic enriched in platelets and bioactive mediators. In urology and sexual medicine, PRP has been promoted for erectile dysfunction (ED) and a growing range of urogenital disorders on the premise that it may support angiogenesis, [...] Read more.
Background/Objectives: Platelet-rich plasma (PRP) is an autologous blood-derived biologic enriched in platelets and bioactive mediators. In urology and sexual medicine, PRP has been promoted for erectile dysfunction (ED) and a growing range of urogenital disorders on the premise that it may support angiogenesis, neuroregeneration, immune modulation, and tissue remodeling. However, clinical uptake has outpaced high-quality evidence, while heterogeneity in PRP preparation, characterization, and delivery limits interpretability and reproducibility. This structured narrative review aims to critically integrate mechanistic, preclinical, and clinical evidence regarding PRP use in ED, Peyronie’s disease (PD), stress urinary incontinence (SUI), interstitial cystitis/bladder pain syndrome (IC/BPS), and selected emerging indications. We further aim to identify sources of heterogeneity and propose an actionable minimum reporting framework (PRP-Uro Checklist) to guide future research. Methods: A structured search of PubMed/MEDLINE was conducted for studies published between 2021 and 2025. The relevant literature on PRP use in ED, PD, SUI, IC/BPS, and related indications was included for critical narrative synthesis. Emphasis was placed on PRP classification and preparation variables, outcome measure validity, and sources of heterogeneity across studies. Results: Mechanistic and preclinical evidence supports PRP’s potential to modulate nerve repair, angiogenesis, extracellular matrix remodeling, and immune polarization through a complex secretome of growth factors, cytokines, and extracellular vesicles (EVs). Clinical evidence suggests that intracavernosal PRP may improve erectile function in selected populations, but effect size, durability, and superiority over placebo remain uncertain due to small trials, substantial placebo effects, short follow-up, and incomplete biologic characterization. Evidence for PRP in PD, SUI, and IC/BPS remains preliminary and is derived largely from small cohorts, proof-of-concept studies, or uncontrolled designs, although early findings suggest potential symptom benefit and acceptable short-term tolerability. Across indications, inconsistent PRP reporting, particularly the absence of absolute platelet dose, leukocyte quantification, activation method, and standardized treatment protocols, represents a major barrier to reproducibility and evidence synthesis. Conclusions: PRP is biologically plausible and appears broadly safe, but its role in urology and sexual medicine remains investigational and is not yet supported by guideline-level evidence. To enhance reproducibility and interpretation, we propose a Minimum PRP Reporting Checklist for Urology and Sexual Medicine Trials (PRP-Uro Checklist). Future progress requires rigorous standardized reporting, indication-specific biologic characterization, rigorously designed sham-controlled trials, clinically meaningful endpoints, and longer-term follow-up. Full article
(This article belongs to the Section Nephrology & Urology)
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13 pages, 1087 KB  
Article
Use of Artificial Intelligence Model Associated with Masson’s Trichrome Staining as a Predictor of Muscle Invasion in Bladder Cancer
by Diego Parrao, Hector Gallegos, Karin Ruz, Román Lay, Catalina Saavedra, Renata Guerrero, Matías Larrañaga, Carolina B. Lindsay and Juan Cristóbal Bravo
Int. J. Mol. Sci. 2026, 27(5), 2237; https://doi.org/10.3390/ijms27052237 - 27 Feb 2026
Viewed by 634
Abstract
Bladder cancer (BC) is the most common malignancy of the urinary tract. Approximately 75% of cases are non-muscle-invasive BC (NMIBC), while muscle-invasive BC (MIBC) and advanced tumors account for most cancer-specific mortality. Accurate assessment of tumor invasion is essential, as staging variability may [...] Read more.
Bladder cancer (BC) is the most common malignancy of the urinary tract. Approximately 75% of cases are non-muscle-invasive BC (NMIBC), while muscle-invasive BC (MIBC) and advanced tumors account for most cancer-specific mortality. Accurate assessment of tumor invasion is essential, as staging variability may lead to inappropriate treatments. Tumor invasion involves several mechanisms including extracellular matrix (ECM) remodeling mediated by metalloproteinases, angiogenesis, and cell adhesions. Masson’s trichrome staining (MTS) provides relevant information on ECM composition. This study evaluated the application of machine learning to MTS-stained bladder biopsies to predict muscle invasion. A retrospective analysis of bladder biopsy images obtained from transurethral resections and cystectomies (2022–2024). A total of 702 histological images were analyzed. A convolutional neural network (CNN) was trained to classify tumors as MIBC or NMIBC and model outputs were correlated with clinical variables. The CNN achieved an accuracy of 95.2% in the training set and 90.1% in validation. Model-derived probabilities were significantly associated with tumor grade, lesion size, and muscle invasion. Logistic regression demonstrated a strong association with invasive disease (OR = 0.07, p = 0.017). CNN-based analysis of MTS-stained bladder biopsy images enable accurate prediction of muscle invasion, with potential to improve diagnostic precision. Full article
(This article belongs to the Special Issue Tumor Markers and Tumor Microenvironment)
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32 pages, 1307 KB  
Review
Catheter-Associated Urinary Tract Infections: Understanding the Interplay Between Bacterial Biofilm and Antimicrobial Resistance
by Desiye Tesfaye Tegegne, Iain J. Abbott and Błażej Poźniak
Int. J. Mol. Sci. 2025, 26(18), 9193; https://doi.org/10.3390/ijms26189193 - 20 Sep 2025
Cited by 9 | Viewed by 9190
Abstract
The increasing use of urinary catheters in healthcare, driven by an aging population and escalating antimicrobial resistance, presents both benefits and challenges. While they are essential to managing urinary retention and enabling precise urine output monitoring, their use significantly increases the risk of [...] Read more.
The increasing use of urinary catheters in healthcare, driven by an aging population and escalating antimicrobial resistance, presents both benefits and challenges. While they are essential to managing urinary retention and enabling precise urine output monitoring, their use significantly increases the risk of catheter-associated urinary tract infections (CAUTIs), the most common type of healthcare-associated infection. CAUTI risk is closely linked to the duration of catheterization and the formation of bacterial biofilms on catheter surfaces. These biofilms, often composed of polymicrobial communities encased in an extracellular matrix, promote persistent infections that are highly resistant to conventional antimicrobial therapies. Common CAUTI uropathogens include E. coli, E. faecalis, P. aeruginosa, P. mirabilis, K. pneumoniae, S. aureus, and Candida spp. The complexity and resilience of these biofilm-associated infections underscore the urgent need for innovative treatment strategies. Therefore, dynamic in vitro bladder infection models, which replicate physiological conditions such as urine flow and bladder voiding, have become valuable tools for studying microbial behavior, biofilm development, and therapeutic interventions under real clinical conditions. This review provides an overview of CAUTIs, explores the role of biofilms in sub-optimal responses to antimicrobial treatment and advances in model systems, and presents promising new approaches to combating these infections. Full article
(This article belongs to the Special Issue Mechanisms in Biofilm Formation, Tolerance and Control: 2nd Edition)
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12 pages, 600 KB  
Article
Expanded Performance Comparison of the Oncuria 10-Plex Bladder Cancer Urine Assay Using Three Different Luminex xMAP Instruments
by Sunao Tanaka, Takuto Shimizu, Ian Pagano, Wayne Hogrefe, Sherry Dunbar, Charles J. Rosser and Hideki Furuya
Diagnostics 2025, 15(14), 1749; https://doi.org/10.3390/diagnostics15141749 - 10 Jul 2025
Viewed by 1494
Abstract
Background/Objectives: The clinically validated multiplex Oncuria bladder cancer (BC) assay quickly and noninvasively identifies disease risk and tracks treatment success by simultaneously profiling 10 protein biomarkers in voided urine samples. Oncuria uses paramagnetic bead-based fluorescence multiplex technology (xMAP®; Luminex, Austin, [...] Read more.
Background/Objectives: The clinically validated multiplex Oncuria bladder cancer (BC) assay quickly and noninvasively identifies disease risk and tracks treatment success by simultaneously profiling 10 protein biomarkers in voided urine samples. Oncuria uses paramagnetic bead-based fluorescence multiplex technology (xMAP®; Luminex, Austin, TX, USA) to simultaneously measure 10 protein analytes in urine [angiogenin, apolipoprotein E, carbonic anhydrase IX (CA9), interleukin-8, matrix metalloproteinase-9 and -10, alpha-1 anti-trypsin, plasminogen activator inhibitor-1, syndecan-1, and vascular endothelial growth factor]. Methods: In a pilot study (N = 36 subjects; 18 with BC), Oncuria performed essentially identically across three different common analyzers (the laser/flow-based FlexMap 3D and 200 systems, and the LED/image-based MagPix system; Luminex). The current study compared Oncuria performance across instrumentation platforms using a larger study population (N = 181 subjects; 51 with BC). Results: All three analyzers assessed all 10 analytes in identical samples with excellent concordance. The percent coefficient of variation (%CV) in protein concentrations across systems was ≤2.3% for 9/10 analytes, with only CA9 having %CVs > 2.3%. In pairwise correlation plot comparisons between instruments for all 10 biomarkers, R2 values were 0.999 for 15/30 comparisons and R2 ≥ 0.995 for 27/30 comparisons; CA9 showed the greatest variability (R2 = 0.948–0.970). Standard curve slopes were statistically indistinguishable for all 10 biomarkers across analyzers. Conclusions: The Oncuria BC assay generates comprehensive urinary protein signatures useful for assisting BC diagnosis, predicting treatment response, and tracking disease progression and recurrence. The equivalent performance of the multiplex BC assay using three popular analyzers rationalizes test adoption by CLIA (Clinical Laboratory Improvement Amendments) clinical and research laboratories. Full article
(This article belongs to the Special Issue Diagnostic Markers of Genitourinary Tumors)
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17 pages, 8827 KB  
Article
Novel Resolvin D1-Loaded Biologics as an Advanced Approach for Inflammation Control and Tissue Regeneration: Preparation and Characterization
by Zhe Xing, Jingwen Liang, Yang Sun, Jing Dai, Jiazheng Cai, Masahito Fujio, Yiwen Xu, Xiaoli An and Ying Xue
Pharmaceutics 2025, 17(5), 643; https://doi.org/10.3390/pharmaceutics17050643 - 13 May 2025
Viewed by 1179
Abstract
Background/Objectives: Constant inflammation can be a detrimental response in bone regeneration. To regulate of the inflammatory response and synchronically promote rapid tissue regeneration is a vital clinical challenge. The urinary bladder matrix (UBM) and small intestinal submucosa (SIS) composite are commonly used extracellular [...] Read more.
Background/Objectives: Constant inflammation can be a detrimental response in bone regeneration. To regulate of the inflammatory response and synchronically promote rapid tissue regeneration is a vital clinical challenge. The urinary bladder matrix (UBM) and small intestinal submucosa (SIS) composite are commonly used extracellular matrix (ECM) materials. We designed a novel drug-loaded membrane by integrating the biological matrix (BM) composed of UBM and SIS composites with Resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, using the lyophilization process. This membrane is referred to as BRL, an acronym for BM-RvD1-Lyophilization. Methods: In this study, the physicochemical properties of the membranes were characterized. Fluorescence staining and the CCK8 assay kit were utilized to assess biocompatibility. To evaluate the inflammatory resolution properties and osteogenic ability of osteoblasts, real-time quantitative PCR and ELISA were conducted. Results: BRL exhibited a more pronounced three-dimensional pore structure, demonstrating excellent physicochemical properties and enabling the slow release of RvD1. This approach improved the viability of MG63 osteoblast-like cells, reduced LPS-induced inflammation, and upregulated osteogenesis-related genes significantly. Conclusions: By integrating inflammation control capabilities into tissue regeneration materials, BRL effectively regulates the tissue regeneration microenvironment, thereby enhancing regeneration efficiency and positioning itself as an exceptional candidate for future tissue regeneration membranes. Full article
(This article belongs to the Section Biologics and Biosimilars)
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7 pages, 3410 KB  
Case Report
Pediatric Reconstruction of Full-Thickness Dog Bite Scalp Avulsion with a Combination of Acellular and Matrix Products: A Case Report
by Francesca Grussu, Guido Ciprandi, Federico Lo Torto, Diego Ribuffo and Mario Zama
Medicina 2024, 60(11), 1838; https://doi.org/10.3390/medicina60111838 - 8 Nov 2024
Cited by 2 | Viewed by 3394
Abstract
The reconstruction of large full-thickness scalp injuries represents a great challenge in pediatric plastic surgery. Epidermal–dermal substitutes come to the rescue when traditional surgical strategies are not suitable. Recently, the new Integra MicroMatrix UBM particulate has arisen on the market. This is an [...] Read more.
The reconstruction of large full-thickness scalp injuries represents a great challenge in pediatric plastic surgery. Epidermal–dermal substitutes come to the rescue when traditional surgical strategies are not suitable. Recently, the new Integra MicroMatrix UBM particulate has arisen on the market. This is an extracellular matrix derived from the porcine urinary bladder matrix (UBM) in which the particulate structure provides close contact to the wound bed. We present the concomitant application of Integra DRT and MicroMatrix for the reconstruction of a full-thickness subtotal scalp defect in a child mauled by a dog. Full article
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16 pages, 275 KB  
Review
Insights into the Interplay between the Urinary Microbiome and Bladder Cancer: A Comprehensive Review
by Rigoberto Pallares-Mendez, Aldo Brassetti, Alfredo Maria Bove and Giuseppe Simone
J. Clin. Med. 2024, 13(16), 4927; https://doi.org/10.3390/jcm13164927 - 21 Aug 2024
Cited by 5 | Viewed by 3356
Abstract
New insights in the urinary microbiome have led to a better understanding being built of the shifts in bacterial representations from health to disease; these hold promise as markers for diagnosis and therapeutic responses. Although several efforts have been made to identify a [...] Read more.
New insights in the urinary microbiome have led to a better understanding being built of the shifts in bacterial representations from health to disease; these hold promise as markers for diagnosis and therapeutic responses. Although several efforts have been made to identify a “core urinary microbiome”, different fingerprints have been identified in men and women that shift with age. The main bacterial groups overall include Firmicutes, Actinobacteria, Fusobacteria, and Bacteroidetes. Although patients with bladder cancer have a microbiome that is similar to that of healthy individuals, differences have been observed at the species level with Fusobacterium nucleatum and Ralstonia, and at the genus level with Cutibacterium. Different bacterial representations may influence extracellular matrix composition, affecting tumor metastatic spreading and tumorigenic metalloproteinase expression. Furthermore, gene expression affecting targets of immune therapy, such as PD-L1, has been associated with changes in bacterial representations and therapeutic response to BCG. This comprehensive review aims to examine the influence of the urinary microbiome in bladder cancer. Full article
(This article belongs to the Special Issue Urological Oncology: New Insights into Diagnosis and Treatment)
13 pages, 3863 KB  
Article
Brain Responses Difference between Sexes for Strong Desire to Void: A Functional Magnetic Resonance Imaging Study in Adults Based on Graph Theory
by Xiaoqian Ying, Yi Gao and Limin Liao
J. Clin. Med. 2024, 13(15), 4284; https://doi.org/10.3390/jcm13154284 - 23 Jul 2024
Cited by 2 | Viewed by 2337
Abstract
Background: The alternations of brain responses to a strong desire to void were unclear, and the gender differences under the strong desire to void remain controversial. The present study aims to identify the functional brain network’s topologic property changes evoked by a strong [...] Read more.
Background: The alternations of brain responses to a strong desire to void were unclear, and the gender differences under the strong desire to void remain controversial. The present study aims to identify the functional brain network’s topologic property changes evoked by a strong desire to void in healthy male and female adults with synchronous urodynamics using a graph theory analysis. Methods: The bladders of eleven healthy males and eleven females were filled via a catheter using a specific infusion and withdrawal pattern. A resting-state functional magnetic resonance imaging (fMRI) was performed on the enrolled subjects, scanning under both the empty bladder and strong desire to void states. An automated anatomical labeling (AAL) atlas was used to identify the ninety cortical and subcortical regions. Pearson’s correlation calculations were performed to establish a brain connection matrix. A paired t-test (p < 0.05) and Bonferroni correction were applied to identify the significant statistical differences in topological properties between the two states, including small-world network property parameters [gamma (γ) and lambda (λ)], characteristic path length (Lp), clustering coefficient (Cp), global efficiency (Eglob), local efficiency (Eloc), and regional nodal efficiency (Enodal). Results: The final data suggested that females and males had different brain response patterns to a strong desire to void, compared with an empty bladder state. Conclusions: More brain regions involving emotion, cognition, and social work were active in females, and males might obtain a better urinary continence via a compensatory mechanism. Full article
(This article belongs to the Special Issue Advanced Imaging Techniques for Nephrology and Urology)
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16 pages, 6181 KB  
Review
Matrix- and Surface-Assisted Laser Desorption/Ionization Mass Spectrometry Methods for Urological Cancer Biomarker Discovery—Metabolomics and Lipidomics Approaches
by Adrian Arendowski
Metabolites 2024, 14(3), 173; https://doi.org/10.3390/metabo14030173 - 20 Mar 2024
Cited by 6 | Viewed by 3721
Abstract
Urinary tract cancers, including those of the bladder, the kidneys, and the prostate, represent over 12% of all cancers, with significant global incidence and mortality rates. The continuous challenge that these cancers present necessitates the development of innovative diagnostic and prognostic methods, such [...] Read more.
Urinary tract cancers, including those of the bladder, the kidneys, and the prostate, represent over 12% of all cancers, with significant global incidence and mortality rates. The continuous challenge that these cancers present necessitates the development of innovative diagnostic and prognostic methods, such as identifying specific biomarkers indicative of cancer. Biomarkers, which can be genes, proteins, metabolites, or lipids, are vital for various clinical purposes including early detection and prognosis. Mass spectrometry (MS), particularly soft ionization techniques such as electrospray ionization (ESI) and laser desorption/ionization (LDI), has emerged as a key tool in metabolic profiling for biomarker discovery, due to its high resolution, sensitivity, and ability to analyze complex biological samples. Among the LDI techniques, matrix-assisted laser desorption/ionization (MALDI) and surface-assisted laser desorption/ionization (SALDI) should be mentioned. While MALDI methodology, which uses organic compounds as matrices, is effective for larger molecules, SALDI, based on the various types of nanoparticles and nanostructures, is preferred for smaller metabolites and lipids due to its reduced spectral interference. This study highlights the application of LDI techniques, along with mass spectrometry imaging (MSI), in identifying potential metabolic and lipid biomarkers for urological cancers, focusing on the most common bladder, kidney, and prostate cancers. Full article
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27 pages, 5062 KB  
Review
Extracellular Matrices as Bioactive Materials for In Situ Tissue Regeneration
by Peng Zhao, Fengbo Yang, Xiaoli Jia, Yuqin Xiao, Chao Hua, Malcolm Xing and Guozhong Lyu
Pharmaceutics 2023, 15(12), 2771; https://doi.org/10.3390/pharmaceutics15122771 - 13 Dec 2023
Cited by 17 | Viewed by 3703
Abstract
Bioactive materials based on a nature-derived extracellular matrix (NECM) represent a category of biomedical devices with versatile therapeutic applications in the realms of tissue repair and engineering. With advancements in decellularization technique, the inherent bioactive molecules and the innate nano-structural and mechanical properties [...] Read more.
Bioactive materials based on a nature-derived extracellular matrix (NECM) represent a category of biomedical devices with versatile therapeutic applications in the realms of tissue repair and engineering. With advancements in decellularization technique, the inherent bioactive molecules and the innate nano-structural and mechanical properties are preserved in three-dimensional scaffolds mainly composed of collagens. Techniques such as electrospinning, three-dimensional printing, and the intricate fabrication of hydrogels are developed to mimic the physical structures, biosignalling and mechanical cues of ECM. Until now, there has been no approach that can fully account for the multifaceted properties and diverse applications of NECM. In this review, we introduce the main proteins composing NECMs and explicate the importance of them when used as therapeutic devices in tissue repair. Nano-structural features of NECM and their applications regarding tissue repair are summarized. The origins, degradability, and mechanical property of and immune responses to NECM are also introduced. Furthermore, we review their applications, and clinical features thereof, in the repair of acute and chronic wounds, abdominal hernia, breast deformity, etc. Some typical marketed devices based on NECM, their indications, and clinical relevance are summarized. Full article
(This article belongs to the Special Issue Bionanomaterials: Fascinating Materials for Biomedical Applications)
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24 pages, 9672 KB  
Article
Design and Validation of a Deep Learning Model for Renal Stone Detection and Segmentation on Kidney–Ureter–Bladder Images
by Zih-Hao Huang, Yi-Yang Liu, Wei-Juei Wu and Ko-Wei Huang
Bioengineering 2023, 10(8), 970; https://doi.org/10.3390/bioengineering10080970 - 16 Aug 2023
Cited by 19 | Viewed by 9541
Abstract
Kidney–ureter–bladder (KUB) imaging is used as a frontline investigation for patients with suspected renal stones. In this study, we designed a computer-aided diagnostic system for KUB imaging to assist clinicians in accurately diagnosing urinary tract stones. The image dataset used for training and [...] Read more.
Kidney–ureter–bladder (KUB) imaging is used as a frontline investigation for patients with suspected renal stones. In this study, we designed a computer-aided diagnostic system for KUB imaging to assist clinicians in accurately diagnosing urinary tract stones. The image dataset used for training and testing the model comprised 485 images provided by Kaohsiung Chang Gung Memorial Hospital. The proposed system was divided into two subsystems, 1 and 2. Subsystem 1 used Inception-ResNetV2 to train a deep learning model on preprocessed KUB images to verify the improvement in diagnostic accuracy with image preprocessing. Subsystem 2 trained an image segmentation model using the ResNet hybrid, U-net, to accurately identify the contours of renal stones. The performance was evaluated using a confusion matrix for the classification model. We conclude that the model can assist clinicians in accurately diagnosing renal stones via KUB imaging. Therefore, the proposed system can assist doctors in diagnosis, reduce patients’ waiting time for CT scans, and minimize the radiation dose absorbed by the body. Full article
(This article belongs to the Special Issue Recent Progress in Biomedical Image Processing)
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16 pages, 7924 KB  
Article
Inhibition of the NF-κB Signaling Pathway Alleviates Pyroptosis in Bladder Epithelial Cells and Neurogenic Bladder Fibrosis
by Jing Chen, Qi Li, Yifan Hong, Xiazhu Zhou, Chengjun Yu, Xiaomao Tian, Jie Zhao, Chunlan Long, Lianju Shen, Shengde Wu and Guanghui Wei
Int. J. Mol. Sci. 2023, 24(13), 11160; https://doi.org/10.3390/ijms241311160 - 6 Jul 2023
Cited by 16 | Viewed by 4098
Abstract
Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the [...] Read more.
Most children with a neurogenic bladder (NB) have bladder fibrosis, which causes irreversible bladder dysfunction and damage to the upper urinary tract. However, the mechanism of bladder fibrosis remains unclear. This study aimed to investigate the underlying causes of bladder fibrosis. Here, the lumbar 6 (L6) and sacral 1 (S1) spinal nerves of Sprague Dawley rats were severed bilaterally to establish NB models. Using RNA-seq, we discovered that the NF-κB signaling pathway and inflammation were upregulated in spinal cord injury (SCI)-induced bladder fibrosis. Subsequent Western blotting, enzyme-linked immunosorbent assays, immunohistochemical staining, and immunofluorescence staining verified the RNA-seq findings. To further clarify whether the NF-κB signaling pathway and pyroptosis were involved in bladder fibrosis, a TGF-β1-treated urinary epithelial cell line (SV-HUC-1 cells) was used as an in vitro model. Based on the results of RNA-seq, we consistently found that the NF-κB signaling pathway and pyroptosis might play important roles in TGF-β1-treated cells. Further experiments also confirmed the RNA-seq findings in vitro. Moreover, using the NLRP3 inhibitor MCC950 rescued TGF-β1-induced fibrosis, and the NF-κB signaling pathway inhibitor BAY 11-7082 effectively rescued TGF-β1-induced pyroptosis and the deposition of extracellular matrix by SV-HUC-1 cells. In summary, our research demonstrated for the first time that the NF-κB signaling pathway inhibition rescued bladder epithelial cells pyroptosis and fibrosis in neurogenic bladders. Full article
(This article belongs to the Special Issue Cell Death in Acute Organ Injury and Fibrosis)
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13 pages, 2122 KB  
Article
Decrease in the Ratio proBDNF/BDNF in the Urine of Aging Female Patients with OAB
by Claudia Covarrubias, Philippe G Cammisotto, Samer Shamout and Lysanne Campeau
Metabolites 2023, 13(6), 723; https://doi.org/10.3390/metabo13060723 - 3 Jun 2023
Cited by 3 | Viewed by 2790
Abstract
Imbalance in the levels of neurotrophins, growth factors crucial in the development, function, and survival of neurons is commonly observed in many pathological states. Concentrations of brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) were measured in the urine of a cohort of [...] Read more.
Imbalance in the levels of neurotrophins, growth factors crucial in the development, function, and survival of neurons is commonly observed in many pathological states. Concentrations of brain-derived neurotrophic factor (BDNF) and its precursor (proBDNF) were measured in the urine of a cohort of aging female patients with overactive bladder disease (OAB). When reported to creatinine, levels were similar between OAB patients and healthy controls. However, the ratio proBDNF/BDNF was significantly decreased in the OAB group. Receiver operating characteristic (ROC) curve analysis of the ratio proBDNF/BDNF displayed a good diagnostic value for OAB (AUC = 0.729). Clinical questionnaires of symptom severity (OABSS and IIQ-7) were negatively correlated with this ratio. On the other hand, microRNAs (miRNA) involved in proBDNF gene translation were expressed at comparable levels between groups. However, urinary enzymatic activity of matrix metalloproteinase-9 (MMP-9), the enzyme that cleaves proBDNF into BDNF, was increased in OAB compared to controls. Levels of miR-491-5p, the main miRNA that downregulates MMP-9 synthesis, were greatly decreased in urine from OAB patients. These results suggest that the ratio proBDNF/BDNF could be useful in the phenotyping of OAB in an aging population, and the difference could originate from enhanced MMP-9 enzymatic activity rather than translational control. Full article
(This article belongs to the Special Issue Crosstalk between Metabolic Syndrome and Voiding Dysfunction)
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18 pages, 4921 KB  
Article
VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma
by Hao-Lun Luo, Yin-Lun Chang, Hui-Ying Liu, Yen-Ting Wu, Ming-Tse Sung, Yu-Li Su, Chun-Chieh Huang, Pei-Chia Wang and Jei-Ming Peng
Int. J. Mol. Sci. 2023, 24(8), 7486; https://doi.org/10.3390/ijms24087486 - 19 Apr 2023
Cited by 10 | Viewed by 3632
Abstract
Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial [...] Read more.
Versican (VCAN), also known as extracellular matrix proteoglycan 2, has been suggested as a potential biomarker in cancers. Previous research has found that VCAN is highly expressed in bladder cancer. However, its role in predicting outcomes for patients with upper urinary tract urothelial cancer (UTUC) is not well understood. In this study, we collected tissues from 10 patients with UTUC, including 6 with and 4 without lymphovascular invasion (LVI), a pathological feature that plays a significant role in determining metastasis. Results from RNA sequencing revealed that the most differentially expressed genes were involved in extracellular matrix organization. Using the TCGA database for clinical correlation, VCAN was identified as a target for study. A chromosome methylation assay showed that VCAN was hypomethylated in tumors with LVI. In our patient samples, VCAN expression was also found to be high in UTUC tumors with LVI. In vitro analysis showed that knocking down VCAN inhibited cell migration but not proliferation. A heatmap analysis also confirmed a significant correlation between VCAN and migration genes. Additionally, silencing VCAN increased the effectiveness of cisplatin, gemcitabine and epirubicin, thus providing potential opportunities for clinical application. Full article
(This article belongs to the Special Issue Cancer Cell Invasion and Metastases 3.0)
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